Abstract
The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD-based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD-based mRNA vaccines encoding binding receptor-binding domain (RBD) of SARS-CoV-2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.